Saturday, 19 September 2015

Schizophrenia and cognitive decline

is attending ISIR15 in person, “en vivo y directo” as us Latins would say. Well, delegates aren’t going to fly all that way just for nothing, are they? Anyway, he is part of the Edinburgh gang, and here is a finding to give us pause: genetic risk for schizophrenia is associated with cognitive decline.

Only last Wednesday I met up with a group of work friends, and the psychiatrist among us, whom I hadn’t seen for quite a while, and who knows nothing of my blogging, replied to my query about her research by spontaneously saying: “I think that the main problem with my schizophrenic patients is low intelligence. Those with higher intelligence seem to deal with it better”. I gave her advance warning of this paper:

Few predictors of people‘s differences in ageing-related cognitive decline have been discovered to date. One potential candidate is genetic risk for schizophrenia, which has previously been linked to cognitive change between childhood and old age in individuals with no schizophrenia diagnosis. To date, no studies have investigated the link between polygenic risk for schizophrenia and cognitive decline within older age.

We used data from longitudinal cognitive testing of subjects from the Lothian Birth Cohorts of 1921 (LBC1921; tests performed at mean ages 79, 83, 87, 90, and 92 years; initial n = 550) and 1936 (LBC1936; tests performed at ages 70, 73, and 76, initial n = 1,091). We examined the association between individual differences in polygenic risk for schizophrenia and differences in the trajectory of cognitive ageing. Polygenic risk scores were derived from the Psychiatric Genomics Consortium‘s most recent GenomeWide Association Study (GWAS) for schizophrenia.

Meta-analysis across both cohorts showed that individuals with higher polygenic risk scores for schizophrenia declined more steeply in their later-life general cognitive ability. These results were significant in the larger LBC1936 study alone. Although the results were in the same direction in LBC1921, they did not reach statistical significance. This work describes a new predictor of greater age-associated cognitive decline. It shows how GWAS results can be useful in predicting ostensibly unrelated phenotypes, and raises important theoretical questions about the links between genetic risk for schizophrenia and lowered intelligence.

Comment: Schizophrenia, in clinical practice, is usually described according to the nature of the disordered thoughts. Yes, disordered thinking is recognised as a great part of the problem, but there is a meta-cognitive dimension: odd thoughts have to be given a reality check, and it seems to be at that stage that many sufferers fail.

Chris Frith studied the condition for many years. Written with Eve Johnson, this is a very good short introduction

Twice in my career I had to deal with an undergraduate becoming schizophrenic. It was frightening - not in the sense that I thought they might take an axe to me, but to see how a human personality could just disintegrate, out of the blue. Moreover, the distress of their parents was so obvious that I had to remind myself not to throw my arms around them and give them a hug. God, what an affliction!